ltiple different biochemical defects have been identified in patients with netic forms of extreme insulin resistance. These defects have included: ) a decreased number of insulin receptors, (2) qualitatively abnormal sulin receptors which are impaired in their ability to couple insulin nding to insulin action; and (3) post-receptor defects in insulin action. ltured Epstein-Bar virus-transformed lymphocytes from insulin resistant tients have been used to study biosynthesis and turnover of insulin ceptors. In those patients with a decreased number of insulin receptors on e cell surface, the rate of receptor degradation is normal. Additional udies show that the decrease in receptor number appears to result from fects in the biosynthetic pathway for receptors. Recent investigations tempt to define the precise biosynthetic defects in individual patients. e insulin receptor possesses an insulin-stimulated tyrosine-specific otein kinase activity which may play a role in mediating insulin action. studies of receptors from insulin resistant patients, there is a general rrelation between the number of insulin receptors (as measured by insulin nding studies) and the tyrosine-kinase activity. However, one patient has en described who appears to have a selective defect in tyrosine-kinase tivity despite possessing a normal number of insulin receptors.